دورية أكاديمية
Efficacy of oleylphosphocholine in experimental cutaneous leishmaniasis.
| العنوان: | Efficacy of oleylphosphocholine in experimental cutaneous leishmaniasis. |
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| المؤلفون: | Van Bocxlaer K; Department of Biology, York Biomedical Research Institute, University of York, York, UK., Dixon J; Department of Biology, York Biomedical Research Institute, University of York, York, UK., Platteeuw JJ; Avivia BV, Novio Tech Campus, Nijmegen, The Netherlands., Van Den Heuvel D; Avivia BV, Novio Tech Campus, Nijmegen, The Netherlands., Mcarthur KN; Pharmidex Pharmaceutical Services Ltd., London, UK., Harris A; Pharmidex Pharmaceutical Services Ltd., London, UK., Alavijeh M; Pharmidex Pharmaceutical Services Ltd., London, UK., Croft SL; London School of Hygiene & Tropical Medicine, Faculty of Infectious and Tropical Diseases, London, UK., Yardley V; London School of Hygiene & Tropical Medicine, Faculty of Infectious and Tropical Diseases, London, UK. |
| المصدر: | The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2023 Jul 05; Vol. 78 (7), pp. 1723-1731. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 7513617 Publication Model: Print Cited Medium: Internet ISSN: 1460-2091 (Electronic) Linking ISSN: 03057453 NLM ISO Abbreviation: J Antimicrob Chemother Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1997- : London : Oxford University Press Original Publication: London, New York, Academic Press. |
| مواضيع طبية MeSH: | Leishmaniasis, Cutaneous*/drug therapy , Leishmaniasis, Cutaneous*/parasitology , Antiprotozoal Agents*/therapeutic use , Leishmaniasis, Visceral*/drug therapy , Leishmania major*, Mice ; Animals ; Phosphorylcholine/therapeutic use ; Mice, Inbred BALB C |
| مستخلص: | Objectives: Cutaneous leishmaniasis (CL) is a neglected tropical disease causing a range of skin lesions for which safe and efficacious drugs are lacking. Oleylphosphocholine (OLPC) is structurally similar to miltefosine and has previously demonstrated potent activity against visceral leishmaniasis. We here present the in vitro and in vivo efficacy of OLPC against CL-causing Leishmania species. Methods: The antileishmanial activities of OLPC were evaluated and compared with miltefosine in vitro against intracellular amastigotes of seven CL-causing species. Following the confirmation of significant in vitro activity, the performance of the maximum tolerated dose of OLPC was evaluated in an experimental murine model of CL followed by a dose-response titration and the efficacy evaluation of four OLPC formulations (two with a fast-release and two with a slow-release profile) using bioluminescent Leishmania major parasites. Results: OLPC demonstrated potent in vitro activity of the same order as miltefosine in the intracellular macrophage model against a range of CL-causing species. A dose of 35 mg of OLPC/kg/day administered orally for 10 days was well-tolerated and able to reduce the parasite load in the skin of L. major-infected mice to a similar extent as the positive control paromomycin (50 mg/kg/day, intraperitoneally) in both in vivo studies. Reducing the dose of OLPC resulted in inactivity and modifying the release profile using mesoporous silica nanoparticles led to a decrease in activity when solvent-based loading was used in contrast to extrusion-based loading, which had no impact on its antileishmanial efficacy. Conclusions: Together, these data suggest that OLPC could be a promising alternative to miltefosine treatment for CL. Further investigations exploring experimental models with additional Leishmania species and skin pharmacokinetic and dynamic analyses are required. (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.) |
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| معلومات مُعتمدة: | MR/P027989/1 United Kingdom MRC_ Medical Research Council |
| المشرفين على المادة: | 0 (oleylphosphocholine) 53EY29W7EC (miltefosine) 0 (Antiprotozoal Agents) 107-73-3 (Phosphorylcholine) |
| تواريخ الأحداث: | Date Created: 20230525 Date Completed: 20230706 Latest Revision: 20230718 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC10320171 |
| DOI: | 10.1093/jac/dkad162 |
| PMID: | 37229566 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1460-2091 |
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| DOI: | 10.1093/jac/dkad162 |